Microwave-Assisted Facile Synthesis of Eu(OH)₃ Nanoclusters with Pro-Proliferative Activity Mediated by miR-199a-3p

As a pharmaceutical excipient, dextran serves as an efficient ligand for stabilizing some clinically available inorganic nanomaterials such as iron oxide nanocrystals. Herein, dextran-capped nanosized europium(III) hydroxides [Eu(OH)₃] nanoclusters (NCs) composed of 5 nm Eu(OH)₃ nanoparticles have been large-scale synthesized via a microwave-accelerated hydrothermal reaction. The as-synthesized Eu(OH)₃ NCs exhibited excellent physiological stability and biocompatibility both in vitro and in vivo and possessed considerable pro-proliferative activities in human umbilical vein endothelial cells (HUVECs). To investigate the epigenetic modulation of Eu(OH)₃ NCs-elicited proliferation, the newly developed high-throughput next generation sequencing technology was employed herein. As a result, we have screened 371 dysregulated miRNAs in Eu(OH)₃ NCs-treated HUVECs and obtained 26 potentially functional miRNAs in promoting cell proliferation. Furthermore, upregulated miR-199a-3p was predicted, validated, and eventually confirmed to be a crucial modulator in the pro-proliferative activity of Eu(OH)₃ NCs by targeting zinc fingers and homeoboxes protein 1 (ZHX1). Importantly, these findings provide potential therapeutic strategy for ischemic heart/limb diseases and tissue regeneration by combination of nanomedicine and gene therapy with Eu(OH)₃ NCs and miR-199a-3p-ZHX1 axis modulation.